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Regenerative-medicine oriented controlling of neuronal cell differentiation with shear stress

Research Project

Project/Area Number 15K06925
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field System genome science
Research InstitutionTokyo University of Science, Yamaguchi (2018-2019)
Keio University (2015-2017)

Principal Investigator

Hiroi Noriko  山陽小野田市立山口東京理科大学, 薬学部, 教授 (20548408)

Co-Investigator(Kenkyū-buntansha) 舟橋 啓  慶應義塾大学, 理工学部(矢上), 准教授 (70324548)
Project Period (FY) 2015-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords再生医療 / マイクロ流体デバイス / 神経細胞分化 / 細胞遊走 / 細胞運命決定 / 神経芽細胞腫 / 液性因子感受性 / 剪断応力 / Wnt3a / 細胞遊走能 / 神経芽腫細胞 / 流れ / ベイズ統計 / マイクロコンタクトプリンティング
Outline of Final Research Achievements

We developed cell culturing devices which can provide various shear stresses to cells. We found that shear stress changes the migration ability, morphologies and the orientation of cells. We also applied the characteristics of microfluidics in the devices for providing humoral stimuli only to a part of a cell instead of a whole cell, by the combination with extracellular matrix arrangement. We also developed a device which can control the concentration gradient of humoral stimuli. We got a biological finding with this device that there exist a quantitative threshold of concentration gradient for the decision of proliferation axis, which strongly connects with the cellular fate.
We developed these cell culturing devices to use shear stress to control neural differentiation for regenerative medicine. New effective medication for neuronal disease are desired by society and the needs will increase. We are planning to use our tools for more practical medication based on the above results.

Academic Significance and Societal Importance of the Research Achievements

剪断応力の神経系の細胞に対する影響を多岐にわたり調査する上で効果的なツールを作成した. これにより, 神経細胞が発生の過程で見せる振る舞いである, 遊走, 配向, 神経細胞間ネットワーキングにおける剪断応力の影響を調べることが可能となった. 同時に, 細胞の一部分という微小領域に限局的に刺激を与える方法として, 本研究成果は実用的な手法の可能性を示している. また神経系に分化する培養細胞において, 細胞運命決定における具体的かつ定量的な, 単細胞スケールでの刺激因子の濃度勾配計測を行った例は本研究が初めてとなる. 以上の様に神経系を人為的に再構成して医療応用するための基礎的な知見を生み出した.

Report

(6 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (16 results)

All 2020 2019 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (11 results) (of which Int'l Joint Research: 8 results,  Invited: 5 results) Funded Workshop (1 results)

  • [Int'l Joint Research] Queen Mary University of London(英国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Neural Differentiation Dynamics Controlled by Multiple Feedback Loops in a Comprehensive Molecular Interaction Network2020

    • Author(s)
      Iwasaki Tsuyoshi、Takiguchi Ryo、Hiraiwa Takumi、Yamada Takahiro G.、Yamazaki Kazuto、Hiroi Noriko F.、Funahashi Akira
    • Journal Title

      Processes

      Volume: 8 Issue: 2 Pages: 166-166

    • DOI

      10.3390/pr8020166

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activation of cell migration via morphological changes in focal adhesions depends on shear stress in MYCN-amplified neuroblastoma cells2019

    • Author(s)
      Hiraiwa Takumi、Yamada Takahiro G.、Miki Norihisa、Funahashi Akira、Hiroi Noriko
    • Journal Title

      Journal of The Royal Society Interface

      Volume: 16 Issue: 152 Pages: 20180934-20180934

    • DOI

      10.1098/rsif.2018.0934

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantitative analysis of sensitivity to a Wnt3a gradient in determination of the pole-to-pole axis of mitotic cells by using a microfluidic device2018

    • Author(s)
      Hiraiwa Takumi、Nakai Yuichiro、Yamada Takahiro G.、Tanimoto Ryuichi、Kimura Hiroshi、Matsumoto Yoshinori、Miki Norihisa、Hiroi Noriko、Funahashi Akira
    • Journal Title

      FEBS Open Bio

      Volume: 8 Issue: 12 Pages: 1920-1935

    • DOI

      10.1002/2211-5463.12525

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Microfluidics application in Quantitative Biology for revealing the origin of Multicellular Organisms2019

    • Author(s)
      Noriko Hiroi
    • Organizer
      Self-organization in multicellular systems
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経分化過程における流れの寄与の解析2019

    • Author(s)
      中村善次、東恩納麻州、平岩巧、山田貴大、広井賀子、舟橋啓
    • Organizer
      定量生物学の会 第9回年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Heat as a signal for cells.2019

    • Author(s)
      広井 賀子
    • Organizer
      Biothermology Workshop 2019
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Quantitative analysis of sensitivity to Wnt3a gradient in determination of the pole-to-pole axis of mitotic cells by using a microfluidic device.2018

    • Author(s)
      Noriko Hiroi
    • Organizer
      Keio University International Symposium on Advanced Technologies for Mechano-biology and Regenerative Medicine.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Quantification of the effect of shear stress on the differentiation of SH-SY5Y cells.2017

    • Author(s)
      東恩納麻州
    • Organizer
      Interantional Workshop on Quantitative Biology 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] High sensitivity to Wnt3a gradient in localization of ODF2/cenexin of neuroblastoma cell in mitosis.2017

    • Author(s)
      平岩巧
    • Organizer
      Interantional Workshop on Quantitative Biology 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Asymmetric division, cell migration, and differentiation control in microfluidic devices.2017

    • Author(s)
      広井賀子
    • Organizer
      Emerging Research Challenges in Biology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] QUANTIFICATION OF THE EFFECT OF SHEAR STRESS ON THE DIFFERENTIATION OF SH-SY5Y CELLS2016

    • Author(s)
      東恩納 麻州
    • Organizer
      International Symposium on Micro-Nano Science and Technology 2016
    • Place of Presentation
      東京大学(東京都、文京区)
    • Year and Date
      2016-12-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 非対称分裂 - 定量で明らかになる組織形成の始まり -2016

    • Author(s)
      広井 賀子
    • Organizer
      医薬工コモンズシンポジウム 第12回インキュベーションラウンジ
    • Place of Presentation
      慶應義塾大学(東京都、新宿区)
    • Year and Date
      2016-07-06
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Development of Method for Asymmetric Cell Division Analysis using Microfluidic Device2016

    • Author(s)
      Takumi Hiraiwa
    • Organizer
      Japan Q-Bio week, Tokyo Symposium
    • Place of Presentation
      東京大学生産技術研究所(東京都目黒区)
    • Year and Date
      2016-01-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of microfluidic cell-collection devise2016

    • Author(s)
      Ayumi Takahashi
    • Organizer
      Japan Q-Bio week, Tokyo Symposium
    • Place of Presentation
      東京大学生産技術研究所(東京都目黒区)
    • Year and Date
      2016-01-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Funded Workshop] International Workshop on Quantitative Biology 20172017

    • Related Report
      2017 Research-status Report

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Published: 2015-04-16   Modified: 2022-02-21  

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